Cytokine release syndrome prophylaxis strategy with dipyrone in patients receiving bispecific Antibodies—Elranatamab, teclistamab, talquetamab and Epcoritamab—at a private hospital in southern Brazil: Preliminary Results

Abstract Introduction Bispecific antibodies have improved progression-free survival and overall survival in relapsed/refractory haematologic malignancies, yet they are frequently associated with cytokine release syndrome (CRS), often necessitating tocilizumab and inpatient care during step-up dosing, thereby increasing treatment costs. Dipyrone (metamizole) is a widely used antipyretic in Brazil and may attenuate the initial inflammatory response when given prophylactically. Objectives To determine whether dipyrone prophylaxis reduces the incidence and severity of CRS and immune-effector-cell–associated neurotoxicity syndrome (ICANS) in patients treated with elranatamab, teclistamab, talquetamab or epcoritamab.Secondary objectives: to analyse infection and cytopenia rates during step-up dosing. Methods Retrospective cohort including all patients who received the above bispecific antibodies between 01 Dec 2022 and 01 Jun 2025 at a private hospital in southern Brazil. Patients with uncontrolled infection at therapy start were excluded. Two groups were compared: fixed dipyrone prophylaxis (1 g PO or IV every 6 h) versus acetaminophen pre-medication only (1 g or 750 mg). Data were extracted from electronic medical records. Results (n = 14): CRS: 0/5 (0 %) in the dipyrone group vs 5/9 (56 %) in the acetaminophen group—grade 1 (11 %), grade 2 (33 %), grade 3 (11 %); no grade ≥ 4 in either group. Tocilizumab use: 0/5 (0 %) with dipyrone vs 4/9 (44 %) with acetaminophen. ICANS: 1/5 (20 %) vs 4/9 (44 %). Infections during step-up: 2/5 (40 %) vs 3/9 (33 %). Neutropenia: 1/5 (20 %) vs 1/9 (11 %). Thrombocytopenia: 1/5 (20 %) vs 0/9 (0 %). Discussion Dipyrone prophylaxis was associated with a markedly lower CRS incidence; none of the five dipyrone-treated patients developed CRS, whereas over half of those on acetaminophen did. Correspondingly, tocilizumab was required in 44 % of acetaminophen patients and in 0 % of the dipyrone group, reinforcing the potential benefit of dipyrone. Reduced CRS and absence of tocilizumab use may improve outpatient feasibility of bispecific therapy, particularly in resource-limited settings. ICANS frequency was also lower with dipyrone (20 % vs 44 %). Infection rates were comparable (40 % vs 33 %), suggesting dipyrone did not heighten infectious risk. Cytopenias appeared somewhat higher with dipyrone (40 % vs 11 %), but small sample size limits conclusions, and toxicity may derive from the bispecifics themselves. Conclusion Preliminary data indicate that dipyrone prophylaxis may lower CRS incidence and eliminate the need for tocilizumab without a clear rise in serious adverse events. Multivariate analyses are in progress. Larger, controlled studies are warranted to confirm these findings and define the role of dipyrone in prophylactic strategies for bispecific antibody therapy.